Gynecological carcinomas such as ovarian carcinoma, cervical carcinoma, endometrial carcinoma and peritoneal carcinoma are among the most frequent causes of cancer death among women in the United States and Europe. It is estimated that ovarian carcinoma alone will be responsible for 14,800 deaths in 1996 in the United States. This dismal outcome is due, at least in part, to an inability to detect the ovarian carcinoma at an early stage of tumor development. When ovarian carcinoma is diagnosed at an early stage, the cure rate approaches 90%. In contrast, the 5 year outlook for women with advanced disease remains poor with no more than a 15% survival rate. Thus, early diagnosis is one of the most effective means of improving the prognosis for ovarian carcinoma.
Transvaginal sonography is the most sensitive of the currently available techniques used for detecting ovarian tumors. However, transvaginal sonography is non-specific, i.e. it will detect benign as well as malignant tumors. Accordingly, detection of an ovarian tumor by transvaginal sonography must be followed by a second diagnostic procedure which is able to distinguish benign tumors from malignant tumors. Moreover, transvaginal sonography is very expensive and, therefore, not useful as a screening procedure for large numbers of patients.
Typically, benign ovarian tumors are distinguished from malignant ovarian tumors by surgical procedures such as biopsy of the mass or aspiration of the mass and cytological examination of the cells that are surgically removed from the patient. However, these techniques are highly invasive, expensive, and in the case of aspiration can lead to release of cancerous cells into the peritoneum.
The antigenic determinant CA 125, which is a high molecular weight mucin-like glycoprotein, is the current serum biomarker of choice for screening for ovarian carcinomas. However, CA 125 testing suffers from two main limitations. First of all, it is not very sensitive. For example, elevated serum CA 125 levels, i.e. levels above the cut-off point of 35 U/ml, are present in fewer than 50% of the patients with Stage I ovarian carcinoma. Taylor, K. J. W. and Schwartz, P. E., "Screening for Early Ovarian Cancer," Radiology, 192:1-10, 1994. In addition, CA 125 testing is not very specific. For example, approximately 25% of patients with benign gynecological diseases also have elevated serum levels of CA 125. Moreover, liver disease such as cirrhosis, even without ascites, elevates serum CA 125 levels above 35 U/ml. Taylor, K. J. W. and Schwartz, P. E., "Screening for Early Ovarian Cancer," Radiology, 192:1-10, 1994.
Accordingly, it would be desirable to have a new, simple, noninvasive or marginally invasive method for detecting gynecological carcinomas, particularly ovarian carcinomas, which is sufficiently sensitive to identify those subjects with early stage ovarian carcinoma, and sufficiently specific to distinguish between benign and malignant gynecological carcinomas.